1. Field of the Invention
The present invention relates to a novel process for producing cyclic thioethers, and more particularly, to novel compounds for producing cyclic thioethers, production processes therefor and methods of use.
2. Background Information
The following processes are known as processes for synthesizing cyclic thioethers.
W. E. Parham et al. in J. Org. Chem., 41, 2628 (1976) disclose a process for synthesizing cyclic thioethers by reacting thiourea with 1-bromo-2-(bromomethyl)benzene and hydrolysis thereof to obtain (2-bromophenyl)methanethiol, and then following lithium-halogen exchange of (2-bromophenyl)methanethiol with butyl lithium, reacting the resulting product with a ketone (G represents NMe or CH2) to obtain mercapto alcohol followed finally by a dehydration reaction with sulfuric acid.
(In the above formula, Bu represents n-butyl, and G represents >CH2 or >NCH3.)
Japanese Patent Application (Kokai) No. Hei 10-182649 discloses a process for synthesizing a cyclic thioether by converting the hydroxyl group of (2-bromophenyl)methanol to a leaving group with a sulfonyl halide such as methanesulfonyl chloride or p-toluenesulfonyl chloride, and after converting to an acetylthio group, removing the acetyl group by hydrolyzing to obtain (2-bromophenyl)methanethiol, and then carrying out a lithium-halogen exchange by reacting with butyl lithium, followed by reacting with a ketone to obtain a mercaptoalcohol compound followed by a dehydration reaction.
(In the above formula, Ac represents acetyl. Bu represents n-butyl, tBu represents tert-butyl, and R represents methyl or p-tolyl.)
Hirokazu Kubota et al., Chem. Pharm. Bull., 46, 242 (1998) disclose a process for synthesizing a cyclic thioether by reacting (2-bromophenyl)methanethiol or 2-(2-bromophenyl)ethanethiol with butyl lithium to carry out a lithium-halogen exchange, followed by reaction of the resulting product with a ketone to obtain a mercapto alcohol and finally carrying out a dehydration reaction with trifluoroacetic acid.
(In the above formula, Bu represents n-butyl, Et represents ethyl, and m represents 1 or 2.)The (2-bromophenyl)methanethiol used as the starting material in the process of Hirokazu Kubota et al. is known to be synthesized by reacting 1-bromo-2-(bromomethyl)benzene with thiourea or derivatives thereof followed by hydrolysis (Overberger et al., J. Amer. Chem. Soc., 78, 666 (1956) and T. Annalisa et al., Farmaco, 45, 617 (1990)), and the process requires at least two steps.
These processes have the disadvantages of requiring two equivalents of organic lithium reagent (resulting in high costs), having a large number of steps and having a low synthetic yield, and none of the processes are suited for industrial production of cyclic thioethers from the viewpoint of economic feasibility.
As a result of conducting extensive studies for the purpose of overcoming these disadvantages and establishing an industrial process for the production of cyclic thioethers, the inventors of the present invention found that cyclic thioethers can be obtained, by going through the compounds of the general formulae (3) and (5), in fewer steps and less expensively than the known processes, thereby leading to completion of the present invention.